Chronic marijuana usage by human pancreas donors is associated with impaired islet function

We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non-users. The islets from marijuana-users displayed reduced insulin secretion as compared to islets from non-users upon stimulation with high glucose (AUC, 3.41 +/- 0.62 versus 5.14 +/- 0.47, p<0.05) and high glucose plus KCI (AUC, 4.48 +/- 0.41 versus 7.69 +/- 0.58, p<0.001). When human islets from chronic marijuana-users were transplanted into diabetic mice, the mean reversal rate of diabetes was 35% versus 77% in animals receiving islets from non-users (p<0.01). Immunofluorescent staining for cannabinoid receptor type 1 (CB1R) was shown to be colocalized with insulin and enhanced significantly in beta cells from marijuana-users vs. non-users (CB1R intensity/islet area, 14.95 +/- 2.71 vs. 3.23 +/- 0.87, p<0.001). In contrast, CB1R expression was not co-localized with glucagon or somatostatin. Furthermore, isolated islets from chronic marijuana-users appeared hypertrophic. In conclusion, excessive marijuana use affects islet endocrine phenotype and function in vitro and in vivo. Given the increasing use of marijuana, our results underline the importance of including lifestyle when evaluating human islets for transplantation or research.

Automated summary

Chronic marijuana use has been found to affect the endocrine phenotype and function of human pancreatic islets, as well as the reversal rate of diabetes in transplantation studies. Islets from marijuana-users displayed reduced insulin secretion and enhanced CB1R expression in beta cells.